The end of 2015 saw a number of stories hailing the productivity of the biopharmaceutical industry for another great year in producing new FDA approved drugs. All drugs, however, have a finite life in terms of exclusivity – the length of time that the innovating company can sell the drug without competition. While 2015 brought us a number of great new medicines, 2016 will see a number of drugs going off patent. The list includes drugs to treat HIV, psychiatric disorders and hypertension. But perhaps most notable are the patent expiries for two major LDL-cholesterol (LDL-c) lowering drugs: the statin, Crestor, from AstraZeneca and the cholesterol absorption inhibitor, Zetia, from Merck.
Anytime a drug becomes generic in the U.S., its price drops dramatically. It is likely that within 12 months, U.S. revenues for both Crestor and Zetia will drop by 90%. That’s to be expected. However, the presence of generic forms for both drugs, rosuvastatin (Crestor) and ezetimibe (Zetia) will have other effects, both commercial and medical. Merck’s Vytorin, a cholesterol lowering drug with sales of over a billion dollars, is actually a combination of ezetimibe and simvastatin (a generic statin originated by Merck’s R&D group). By combining two complementary ways of lowering LDL-c in a single pill, Vytorin offers physicians a simple way of lowering LDL-cholesterol in their heart disease patients. But payers don’t really care about convenience. They are focused on containing costs. Last year, a 30 day prescription of Zetia cost roughly $300, similar to the cost of 30 days of Vytorin. However, it is reasonable to expect that the cost of 30 days of the generic ezetimibe will be less than $10. Given that the 30 day cost of simvastatin, the other component of Vytorin, is even less than that, payers will reject prescription requests for Vytorin and require patients to take each drug individually. This will certainly be less convenient for both patients and physicians. But, by changing from $300 for a 30 day supply of Vytorin to perhaps as low as $10 for 30 days of both ezetimibe and simvastatin, payers will save millions of dollars.
However, the availability of generic ezetimibe and rosuvastatin could have other impacts. There are a number of people who cannot tolerate statins because of side-effects such as muscle pain. Statin intolerance, in fact, is a driver for companies seeking novel LDL-c lowering drugs in order to provide patients with alternatives. But that road has gotten harder. Interestingly, statin intolerance may be able to be overcome in some patients by stopping statin treatment for a brief period, then restarting therapy. Thus, payers will urge that multiple statins be tried before confirming a statin intolerance diagnosis. If all of that doesn’t work, then ezetimibe use will be encouraged as this will be as cheap as statins. These prescribing patterns will shrink the “statin intolerant” patient pool, thus narrowing the heart patient population eyed by Esperion for its novel LDL-c lowering drug, ETC-1002.
But the most compelling new LDL-c drugs are the PCSK-9 inhibitors Praluent (Sanofi/Regeneron ) and Repatha (Amgen). These medicines have the ability to lower LDL-c to levels unattainable by statins alone. Theoretically, the availability of the new generic drugs should have little impact on the sales of PCSK-9 drugs. However, the developers of these drugs have yet to prove that heart patients have better survival with LDL-c levels at 45mg/dL than 70mg/dL., although such data may be available in the next 24 months. The PCSK-9 inhibitors are expensive drugs listing at more than $14,000/year/patient. Payers will seek to have heart patients and their physicians try a variety alternatives, such as combining rosuvastatin and ezetimibe, to lower LDL-c before turning to the PCSK-9s. If a patient can get their LDL-c below 70mg/dL using a combination of drugs costing less than $1 dollar/day, that combination will be used long before allowing access to the more expensive drugs.
There is no doubt that the loss of exclusivity for Crestor and Zetia will impact the bottom lines of AstraZeneca and Merck, respectively. But the availability of the generic forms of these drugs will also have an impact on physician prescribing habits and even drugs not yet on the market. Containing prescription drug costs is a major priority these days, and the use of generics is a key lever in accomplishing this, particularly in the face of high costs alternatives
